Binding mechanisms are extremely important for protein function. Through molecular dynamics simulations, we study the path from the open to the closed form in a protein for which there are experimental data for a large conformational change. For several enzymes we have studied, a series of events emerges, consistent with experiment and with a striking correlation between conserved database positions and identified flexible regions. Despite the dissimilar structure, and function, we observe a conserved mechanism. Proteins function through binding. Our goal is to predict binding modes of protein-protein and protein-ligand sociations. Further, our goal is to predict these even if there are significant structural changes, or if the input are modeled (genomic) data. Our work is in two directions. First, to characterize binding sites in a way that is immune to the fine features of the molecular surface. And second to devise flexible docking algorithms. For the first, we study residue "hot spots" on the protein surface and explore combinatorial phage display libraries. For the second, we continue the development of docking algorithms which allow hinge-bending motions.